Bacterial outer membrane vesicle based versatile nanosystem boosts the efferocytosis blockade triggered tumor-specific immunity

Efferocytosis inhibition is emerging as an attractive strategy for antitumor immune therapy because of the subsequent leak of abundant immunogenic contents. However, the practical efficacy is seriously impeded by the immunosuppressive tumor microenvironments. Here, we construct a versatile nanosystem that can not only inhibit the efferocytosis but also boost the following antitumor immunity. MerTK inhibitor UNC2025 is loaded into the bacterial outer membrane vesicles (OMVs), which are then modified with maleimide (mU@OMVs). The prepared mU@OMVs effectively inhibits the efferocytosis by promoting the uptake while preventing the MerTK phosphorylation of tumor associated macrophages, and then captures the released antigens through forming universal thioether bonds. The obtained in situ vaccine effectively transfers to lymph nodes by virtue of the intrinsic features of OMVs, and then provokes intense immune responses that can efficiently prevent the growth, metastasis and recurrence of tumors in mice, providing a generalizable strategy for cancer immunotherapy.

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March 2021
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No statistical methods were used to determine sample sizes. Sample sizes were primarily determined by the availability of data or on the basis of previous experimental experience (Adv. Mater., 2021, 33, e2005562; Angew. Chem. Int. Ed., 2020, 59, 406). In vitro experiments were performed with at least 3 biologically independent samples. All in vivo experiments were performed with at least 3 independent animals. Sample sizes were sufficient to perform statistical analyses.
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